A broad-based series of studies in clinical psychopharmacology is being proposed, which will include screening of antipsychotic, antidepressant and antianxiety drugs, testing the therapeutic applications of marihuana and its derivatives, and employing drugs as tools for better understanding the chemical nature of these disorders. The emphasis will now be on exploratory clinical trials of new approaches to treatment. Antipsychotic drugs will be chosen on the basis of their not being closely related chemically or pharmacologically to current drugs, or from those showing special types of actions. A clinical trial of thyrotropin-releasing hormone will be undertaken in depression. Very potent sedatives will be tried in an attempt to separate sedative from antianxiety effects. Marihuana will be tested initially in depressions and in migraine. The clinical pharmacology of levodopa in schizophrenia will be explored, to try to verify our previous observations that it exacerbates the disorder. Later, the clinical pharmacology of apomorphine will be studied for the same purpose. In the case of some treatments, controls of various sorts will be used, including the traditional blind controlled trial, with variations suitable to the particular problem being investigated. Laboratory studies appropriate to each clinical study will be done concomitantly, including some studies of the pharmacokinetics of various drugs of interest. This new program will represent a departure from our past work in that we shall no longer look at conventional drugs and potential specific areas of actions for them.